Department of Clinical Microbiology & Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel.
Mamm Genome. 2022 Sep;33(3):421-436. doi: 10.1007/s00335-022-09948-x. Epub 2022 Feb 3.
Type 2 diabetes (T2D) is a polygenic and multifactorial complex disease, defined as chronic metabolic disorder. It's a major global health concern with an estimated 463 million adults aged 20-79 years with diabetes and projected to increase up to 700 million by 2045. T2D was reported to be one of the four leading causes of non-communicable disease (NCD) deaths in 2012. Environmental factors play a part in the development of polygenic forms of diabetes. Polygenic forms of diabetes often run-in families. Fortunately, T2D, which accounts for 90-95% of the entire four types of diabetes including, Type 1 diabetes (T1D), T2D, monogenic diabetes syndromes (MGDS), and Gestational diabetes mellitus, can be prevented or delayed through nutrition and lifestyle changes as well as through pharmacologic interventions. Typical symptom of the T2D is high blood glucose levels and comprehensive insulin resistance of the body, producing an impaired glucose tolerance. Impaired glucose tolerance of T2D is accompanied by extensive health complications, including cardiovascular diseases (CVD) that vary in morbidity and mortality among populations. The pathogenesis of T2D varies between populations and/or ethnic groupings and is known to be attributed extremely by genetic components and environmental factors. It is evident that genetic background plays a critical role in determining the host response toward certain environmental conditions, whether or not of developing T2D (susceptibility versus resistant). T2D is considered as a silent disease that can progress for years before its diagnosis. Once T2D is diagnosed, many metabolic malfunctions are observed whether as side effects or as independent comorbidity. Mouse models have been proven to be a powerful tool for mapping genetic factors that underline the susceptibility to T2D development as well its comorbidities. Here, we have conducted a comprehensive search throughout the published data covering the time span from early 1990s till the time of writing this review, for already reported quantitative trait locus (QTL) associated with murine T2D and comorbidities in different mouse models, which contain different genetic backgrounds. Our search has resulted in finding 54 QTLs associated with T2D in addition to 72 QTLs associated with comorbidities associated with the disease. We summarized the genomic locations of these mapped QTLs in graphical formats, so as to show the overlapping positions between of these mapped QTLs, which may suggest that some of these QTLs could be underlined by sharing gene/s. Finally, we reviewed and addressed published reports that show the success of translation of the identified mouse QTLs/genes associated with the disease in humans.
2 型糖尿病（T2D）是一种多基因和多因素的复杂疾病，定义为慢性代谢紊乱。它是一个主要的全球健康问题，据估计，20-79 岁的成年人中有 4.63 亿人患有糖尿病，到 2045 年预计将增加到 7 亿。2012 年，T2D 被报道为四种主要的非传染性疾病（NCD）死亡原因之一。环境因素在多基因糖尿病形式的发展中起作用。多基因糖尿病形式往往在家庭中出现。幸运的是，2 型糖尿病（T2D），占四种糖尿病类型（包括 1 型糖尿病（T1D）、2 型糖尿病、单基因糖尿病综合征（MGDS）和妊娠糖尿病）的 90-95%，可以通过营养和生活方式的改变以及药物干预来预防或延迟。T2D 的典型症状是高血糖水平和全身胰岛素抵抗，导致葡萄糖耐量受损。T2D 的葡萄糖耐量受损伴随着广泛的健康并发症，包括心血管疾病（CVD），其发病率和死亡率在不同人群中有所不同。T2D 的发病机制在不同人群和/或种族群体之间有所不同，已知与遗传成分和环境因素密切相关。显然，遗传背景在决定宿主对某些环境条件的反应方面起着关键作用，无论是否发展为 T2D（易感性与抗性）。T2D 被认为是一种无声的疾病，在诊断前可能会持续多年。一旦诊断出 T2D，就会观察到许多代谢功能障碍，无论是作为副作用还是作为独立的合并症。小鼠模型已被证明是一种强大的工具，可用于绘制遗传因素图谱，这些遗传因素决定了对 T2D 发展及其合并症的易感性。在这里，我们对从 20 世纪 90 年代初到撰写本综述这段时间内发表的数据进行了全面搜索，以寻找已报道的与不同小鼠模型中的 T2D 及其合并症相关的定量性状基因座（QTL）。这些小鼠模型包含不同的遗传背景。我们的搜索结果发现了 54 个与 T2D 相关的 QTL 和 72 个与该疾病相关的合并症相关的 QTL。我们以图形格式总结了这些映射 QTL 的基因组位置，以显示这些映射 QTL 之间的重叠位置，这可能表明其中一些 QTL 可能是由共享基因/等位基因引起的。最后，我们回顾并讨论了已发表的报告，这些报告显示了已识别的与疾病相关的小鼠 QTL/基因在人类中的成功转化。
